| Author/Editor | Šelb, Julij; Rijavec, Matija; Eržen, Renato; Zidarn, Mihaela; Kopač, Peter; Škerget, Matevž; Bajrović, Nisera; Demšar Luzar, Ajda; Park, Young Hwan; Liu, Yihui; Čurin-Šerbec, Vladka; Zver, Samo; Košnik, Mitja; Lyons, Jonathan J.; Korošec, Peter | |
| Title | Routine KIT p.D816V screening identifies clonal mast cell disease in Hymenoptera allergic patients regularly missed using baseline tryptase levels alone | |
| Type | članek | |
| Vol. and No. | Letnik 148, št. 2 | |
| Publication year | 2021 | |
| Volume | str. 621-626.e7 | |
| ISSN | 1097-6825 - The Journal of allergy and clinical immunology | |
| Language | eng | |
| Abstract | Background. Clonal mast cell disorders and elevated BST of unknown cause(s) are associated with severe Hymenoptera venom-triggered anaphylaxis (HVA). However, some individuals with clonal disease have normal BST (<11.4 ng/mL). Objective. To evaluate whether screening for KIT p.D816V in the blood is a useful clinical tool to risk-stratify patients with venom allergy. Methods. We prospectively recruited 374 patients with Hymenoptera allergy and no overt signs of mastocytosis referred to our center in the years 2018-19. KIT p.D816V was determined in the peripheral blood with qPCR and tryptase genotyping was performed by droplet-digital PCR. Results. 351 patients (93.9%) had normal levels of BST and KIT p.D816V was detected in 8% of patients (28/351), predominantly in patients with the most severe Mueller grade IV anaphylaxis (18.2%[24/132] vs 1.8%[4/88 in grade III; 0/131 in other grades] in lower grades; P<0.001). In grade IV patients with normal BST, KIT p.D816V was associated with more severe symptoms including a significantly higher frequency of loss of consciousness (58.3%[14/24] vs 34.3%[37/108]; P=0.03) and absence of skin symptoms (41.7%[10/24] vs 15.7%[17/108]; P=0.004). Among patients with normal BST, KIT p.D816V (OR [95%CI]: 10.25[3.75-36.14]; P<0.0001) was the major risk factor associated with severe HVA. Hereditary [alpha]-tryptasemia (H[alpha]T), due to increased germline copies of TPSAB1 encoding [alpha]-tryptase was the most common cause (65.2%; 15/23) of elevated BST in patients with HVA and together with KIT p.D816V accounted for 90% (20/23) of BST elevations in HVA patients. Conclusion. These results indicate that routine KIT p.D816V screening identifies clonal disease in high-risk HVA patients regularly missed using BST alone. | |
| Descriptors | Anaphylaxis Venoms Hypersensitivity Mast cells Anafilaksija Živalski strupi Preobčutljivost Mastociti | |
| Keywords | hereditarna alfa-triptazemija hereditary alpha-tryptasemia |